Gamma activity in the piriform cortex and behavioral thresholds for electrical stimulation in the olfactory bulb

Our understanding of the molecular and genetic etiologies of allergic disorders, which affect 20%-30% of the general population, has greatly improved over the past several years. Previously, research focused on examination of immediate hypersensitivity reactions, initiated by the cross-linking of IgE molecules on the surface of mast cells/basophils, resulting in the release of a host of mediators, which cause symptoms typified by acute anaphylaxis. Although there has been substantial progress in understanding the molecular biology of mast cell and basophil activation and of the regulation of IgE synthesis, recent studies have shifted attention to the cellular and molecular mechanisms that cause a broader allergic inflammatory response and underlie the more chronic and severe symptoms of allergy and asthma. In this report, we will review a substantial body of recent experimental work that has provided the basis for our new understanding of the allergic inflammatory response and the pathogenesis of allergic diseases. We will describe the recent progress in defining the immunological basis for allergic disease, and how subsets of helper CD4+ T cells secreting a specific array of cytokines (Th2 cytokines) regulate/cause allergic inflammation. We will review the cell biology of Th2 cells, the role of Th2 cells in allergic disease, and biological, genetic, and therapeutic mechanisms that influence the differentiation of CD4+ T cells and enhance or suppress cytokine synthesis in Th2 cells. These mechanisms control the expression of allergic diseases, which occur in some but not all individuals following environmental exposure to allergens.     

Some effects of conditioned aversion on food intake and olfactory bulb electrical responses in the rat

Rats maintained on an unadulterated synthetic food, available from 8 a.m. to 10 a.m. everyday, were submitted to an aversive conditioning schedule on which a first ingestion of eucalyptol-flavored food (EF) was followed by an apomorphine injection (20 mg/kg, ip). In the first experiment the daily food intake was measured from Day 1 to 17, during the first and second hours of the meal. The EF was offered on Days 8, 9, and 17 during the first or the second hour of the meal (Series B or A). On Day 8, the meal was followed in a group of rats by the apomorphine injection. As compared with the intake of Day 8, the mean EF intake of Day 9 was significantly decreased in Series A and B, and of Day 17 in Series A only. No significant EF-intake modification could be observed in a saline-injected group or in an untreated control group. In the second experiment, rats bearing bulbar electrodes for the chronic recording of multiunit mitral cell responses received a 2-hr EF meal before the apomorphine injection. They were stimulated by puffs of odors of pure eucalyptol, unadulterated food, and EF and recorded in hungry and satiated states. Before the aversive conditioning, a significantly greater occurrence of positive responses to the odors of unadulterated food and EF was observed in hungry rats compared with satiated rats. The eucalyptol odor yielded equivalent patterns of responses in hungry and satiated rats before and after conditioning. Conditioning did not alter the modulated responses to unadulterated food odor (a greater occurrence of positive responses was still observed in hungry rats) but modified the responses to the odor of EF (the same high rate of positive responses was then observed in satiated and hungry rats). Electrophysiological data are discussed in terms of palatability changes and food-odor meaning.     

Noradrenergic neuromodulation in the olfactory bulb modulates odor habituation and spontaneous discrimination.

Noradrenergic projections from the locus coeruleus (LC) project to the olfactory bulb (OB), a cortical structure implicated in odor learning and perceptual differentiation among similar odorants. The authors tested the role of OB noradrenaline (NA) in short-term olfactory memory using an animal model of LC degeneration coupled with intrabulbar infusions of NA. Specifically, the authors lesioned cortical noradrenergic fibers in mice with the noradrenergic neurotoxin N-Ethyl-N-(2-chloroethyl)-2-bromobenzylamine hydrochloride (DSP4) and measured the effects on an olfactory habituation/spontaneous discrimination task. DSP4-treated mice failed to habituate to repeated odor presentations, indicating that they could not remember odors over the 5-min intertrial interval. The authors then infused NA bilaterally into the OBs of both DSP4-treated and nonlesioned control animals at two concentrations (10-3M and 10-5M, 2 μl/side). In DSP4-treated animals, NA administration at either concentration restored normal habituation and spontaneous discrimination performance, indicating that noradrenergic neuromodulation mediates these aspects of perceptual learning and that its efficacy does not require activity-dependent local regulation of NA release. Functional OB learning mechanisms may be necessary for normal odor recognition and differentiation among physically similar odorants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopaminergic modulation of olfactory bulb processing affects odor discrimination learning in rats.

Olfactory behavioral studies have shown that, when modulated through systemic injections, D1 and D2 receptors have opposing effects on odor discrimination learning. In the present study, cannulated male Sprague–Dawley rats were used to investigate how the modulation of these 2 types of dopaminergic receptors through direct infusion of D1/D2 agonists and antagonists into the olfactory bulb affect olfactory perception. Dopaminergic modulation was locally altered by manipulations of D1 (agonist SKF 82958: 14.6, 43.8, & 143.6 mM; antagonist SCH-23390: 13.4, 40.1, & 60.1 mM) and D2 (agonists quinpirole: 78.2, 117.3, & 156.4 mM; antagonist sulpiride: 0.3, 0.9, & 2.9 mM) receptors during a simultaneous odor discrimination task. The authors found that modulation of D2, but not D1, receptors significantly affected rats’ odor discrimination performance. A significant positive correlation between blockade of D2 receptors and discrimination performance, as well as a significant negative correlation between D2 receptor activation and discrimination performance, was observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory bulb habituation to odor stimuli.

Habituation is a simple form of memory, yet its neurobiological mechanisms are only beginning to be understood in mammals. In the olfactory system, the neural correlates of habituation at a fast experimental timescale involving very short intertrial intervals (tens of seconds) have been shown to depend on synaptic adaptation in olfactory cortex. In contrast, behavioral habituation to odorants on a longer timescale with intertrial intervals of several minutes depends on processes in the olfactory bulb, as demonstrated by pharmacological studies. We here show that behavioral habituation to odorants on this longer timescale has a neuronal activity correlate in the olfactory bulb. Spiking responses of mitral cells in the rat olfactory bulb adapt to, and recover from, repeated odorant stimulation with 5-min intertrial intervals with a time course similar to that of behavioral habituation. Moreover, both the behavioral and neuronal effects of odor habituation require functioning N-methyl-d-aspartic acid receptors in the olfactory bulb. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of conditioned odor aversion by entorhinal cortex lesions in the rat.

This study examined the role of the entorhinal cortex (EC) in conditioned odor aversion learning (COA). Lateral EC lesions did not impair but rather facilitated COA. In the experiments the delay separating the odor cue presentation from the subsequent toxicosis was varied during acquisition. EC-lesioned rats demonstrated COA for delays up to 2 hr, whereas sham-operated rats displayed COA only if toxicosis immediately followed the odor cue. This facilitation was not dependent on the intensity of the odor and corresponded to a facilitated long-delay learning. EC lesion did not affect conditioned taste aversion, confirming that the facilitation effect does not correspond to a general facilitation of conditioned aversion learning. Taken together, these results indicate that the removal of the EC may allow odor-toxicosis associations across longer delays by extending the duration of the olfactory trace. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective involvement of the lateral entorhinal cortex in the control of the olfactory memory trace during conditioned odor aversion in the rat.

Evidence from the effect of aspiration lesions of the entorhinal cortex (EC) has shown that this region is involved in conditioned odor-aversion (COA) learning-that is, the avoidance of an odorized tasteless solution the ingestion of which precedes toxicosis-by rendering COA tolerant to long odor-toxicosis delay. The present study examined whether neurotoxic lesions restricted to the lateral or medial parts of the EC, in comparison with large aspiration lesions, were sufficient to produce this effect. Male Long-Evans rats received odor-intoxication pairing with either a short (5-min) or long (120-min) delay between the presentation of the odor and toxicosis. All groups, including sham-lesioned controls, showed COA at the 5-min odor-toxicosis delay interval, but only rats with lateral EC damage displayed COA at the longer delay. These data show that the lateral EC is part of the substrate involved in the control of the olfactory memory trace during COA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arousal response to electrical stimulation of the cerebral cortex in cats.

Questions the belief that the arousal response produced by stimulation at various sites in the cortex is due to direct stimulation of the cortical component of a central arousal system. 3 observations of 9 female and 2 male cats were not consistent with this interpretation. Fractionation of the arousal response, subtotal parts of the reaction being produced by varying the intensity of cortical stimulation, occurred only when the S was in the resting state, and the arousal response habituated during repeated cortical stimulation. These observations on the arousal response to cortical stimulation were duplicated closely by the arousal response to an auditory stimulus. In agreement with a 1967 study by H. Ursin, K. Wester, and R. Ursin, it is suggested that the arousal response to stimulation of the cortex is a reflex to a sensory experience created by cortical stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropeptide FF receptors of mouse olfactory bulb: binding properties and stimulation of adenylate cyclase activity

Neuropeptide FF (NPFF) receptors have been characterized in mouse olfactory bulb membranes by using [125I][1DMe]Y8Fa. The specific binding of this NPFF analogue was time and concentration dependent, reversible, saturable, and of high affinity (Kd = 0.022 nM, Bmax = 56.4 fmol/mg protein). In olfactory bulb membranes, NaCl increased the affinity of [125I][1DMe]Y8Fa by decreasing the dissociation rate constant (k-1). In contrast, the nonhydrolyzable analogue of GTP, Gpp[NH]p, decreased the maximal number of binding sites suggesting a coupling of NPFF receptors to a G-protein. In mouse olfactory bulb and spinal cord membranes, NPFF analogues stimulated adenylate cyclase activity in a time- and dose-dependent manner, whereas in the cerebellum, which does not possess NPFF receptors, low cAMP production was stimulated by NPFF. Our data are consistent with guanine nucleotide binding protein regulation of NPFF receptors positively coupled to adenylate cyclase.     

Role of G protein betagamma subunits in muscarinic receptor-induced stimulation and inhibition of adenylyl cyclase activity in rat olfactory bulb

In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic AMP, enhancing basal and Gs-stimulated adenylyl cyclase activities and inhibiting the Ca2+/calmodulin- and forskolin-stimulated enzyme activities. In the present study, we investigated the involvement of G protein betagamma subunits by examining whether the muscarinic responses were reproduced by the addition of betagamma subunits of transducin (betagamma(t)) and blocked by putative betagamma scavengers. Membrane incubation with betagamma(t) caused a stimulation of basal adenylyl cyclase activity that was not additive with that produced by carbachol. Like carbachol, betagamma(t) potentiated the enzyme stimulations elicited by vasoactive intestinal peptide and corticotropin-releasing hormone. RT-PCR analysis revealed the expression of mRNAs encoding both type II and type IV adenylyl cyclase, two isoforms stimulated by betagamma synergistically with activated Gs. In addition, betagamma(t) inhibited the Ca2+/calmodulin- and forskolin-stimulated enzyme activities, and this effect was not additive with that elicited by carbachol. Membrane incubation with either one of two betagamma scavengers, the GDP-bound form of the alpha subunit of transducin and the QEHA fragment of type II adenylyl cyclase, reduced both the stimulatory and inhibitory effects of carbachol. These data provide evidence that in rat olfactory bulb the dual regulation of cyclic AMP by muscarinic receptors is mediated by betagamma subunits likely acting on distinct isoforms of adenylyl cyclase.     

Changes in the motor response threshold to direct electric stimulation of the motor cortex during elaboration of conditioned reflex switching-over

During elaboration of switching-over of an alimentary salivary conditioned reflex to a defensive one in dogs, with foreleg passive flexion as a signal stimulus, excitability changes of opposite signs appeared in the cortical representation of the left foreleg. At the stage of elaborated switching-over, the threshold of the flexor reaction to a direct stimulation of the motor cortex became lower in the alimentary experimental situation (passive rise--milk) and rose in the defensive situation (passive rise--acid).     

Contribution of mechanical activity and electrical activity to cellular electrical uncoupling in ischemic rabbit papillary muscle

We separated mechanical and electrical activity during ischemia and we assessed the contribution of each of these variables to ischemia induced cellular electrical uncoupling. In two groups of rabbit papillary muscles, mechanical and electrical activity at the onset of ischemia was abolished. We determined how this affected the time of onset of uncoupling. Also, action potential duration (APD80), conduction velocity and extracellular pH were recorded. In the first group, the BDM group, mechanical arrest was achieved with 10 mM BDM (2,3-butanedione monoxime). This had no effect on APD80 and conduction velocity. In the second group, the quiescent group, electrical as well as mechanical arrest was obtained by not stimulating the muscles. The effect of electrical arrest was estimated as the difference between this group and the BDM group. Mechanical arrest delayed uncoupling significantly (control: 14.6 +/- 0.9 (min), mean +/- S.E.M., n = 10; BDM: 19.3 +/- 1.1, n = 10; P < 0.025). Electrical arrest caused an even greater delay (quiescent: 41.6 +/- 4.6, n = 7; P < 0.001 v control and BDM). In the BDM group, these effects were not associated with a difference of APD80 during ischemia, but with a smaller decrease of conduction velocity. Delay of uncoupling correlated with delay of extracellular acidosis. We conclude: (1) mechanical and electrical activity both are significant determinants of ischemia induced uncoupling; (2) delay of uncoupling is associated with delay of extracellular acidosis, indicating a reduced rate of metabolism.     

Alcohol aversion generalization in rats: Specific disruption of taste and odor cues with gustatory neocortex or olfactory bulb ablations.

Rats with ablations of the gustatory neocortex (Experiment 1) and rats with olfactory bulb ablations (Experiment 2) were compared with normal rats for aversion generalization to both single taste solutions (sucrose, sodium chloride, quinine hydrochloride, hydrochloric acid) and compound taste solutions (pairs of the four single tastants) following alcohol aversion training. All rats acquired equal and strong alcohol aversions. Control rats showed consistent aversion generalization to both the sucrose plus quinine and the sucrose plus hydrochloric acid solutions; no significant generalization occurred to the single tastants except a weak generalization to sucrose in Experiment 2. Rats with gustatory neocortical ablations failed to show aversion generalization to any of the taste solutions. Rats with olfactory bulbectomies displayed the same aversion generalization functions as control rats but exhibited significantly faster extinction of the alcohol aversion than did the trained control rats. Results from the present experiments suggest that during alcohol aversion learning, rats lacking gustatory neocortex use odor cues (no taste generalization), whereas rats lacking olfactory bulbs utilize taste cues (normal taste generalization). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus.

Stimulating electrodes were implanted in rabbit cerebellum, providing an electrical conditioned stimulus (CS) activating cortical parallel fibers and thence Purkinje and other cells, and an electrical unconditioned stimulus (US) activating underlying white matter and eliciting unconditioned responses. Paired CS-US presentations led to the development of conditioned responses, which showed extinction following CS-alone trials and reacquisition with significant savings on reinstatement of paired trials. Increased local excitability as a result of paired training (but not following unpaired stimulus presentations) was observed in cerebellar cortex, as manifested in substantial decreases in CS threshold for response elicitation in all subjects. This preparation offers a model for the study of plastic neuronal interactions within cerebellar networks critically involved in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of olfactory bulb removal on ingestive behaviors, activity levels and self-stimulation in hamsters.

Examined the influence of olfactory bulb removal on running activity, body weight, food and water consumption, and lateral hypothalamic self-stimulation rates in 24 male and 4 female golden hamsters. 2 experiments were conducted in an attempt to characterize more completely the behavioral and physiological deficits which might be related to the total abolition of male sexual behavior produced by ablation of the olfactory bulbs. This operation depressed food consumption and body weight during the 1st 5-10 postoperative days only and had no effect on water intake. During the same postoperative period, running activity declined by 50% before returning to normal. Self-stimulation rates were reduced below normal during the 1st 2 postoperative days but returned to preoperative levels by 7 days. These transient effects of bulbectomy on the measured variables were contrasted with the permanent deficit in male sexual behavior which results from olfactory bulb removal. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predicting odorant quality perceptions from multidimensional scaling of olfactory bulb glomerular activity patterns.

Odorants and their perceptions differ along multiple dimensions, requiring that a critical examination of any putative neural code directly assess the multidimensional nature of the encoding process. Previous work has examined simple, systematic odorant differences that, regardless of coding strategy, would be expected to produce simple, systematic predictions in neural and behavioral responses. In the present study, an odorant identification confusion matrix task that extracts precise quality relationships across odorants was used to determine whether spatially specific glomerular activity patterns predict perceptual quality relationships for odorants that cannot easily be classified a priori along a single chemical dimension. Multidimensional scaling (MDS) analysis of odorant pattern similarity measures derived from the comparison of [14C]-2-deoxyglucose glomerular activity pattern data yielded a two-dimensional odorant activity space that was highly significantly predictive of similarly obtained odorant perceptual spaces, uniformly across animals. These results strongly support the relevance of global spatial patterns in the olfactory bulb to the encoding of odor quality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retrograde transport of nerve growth factor from olfactory bulb to olfactory epithelium

OBJECTIVE: The purposes of this study were to determine if splenic perfusion measurements obtained using dynamic CT are useful in the evaluation of portal hypertension. MATERIALS AND METHODS: Forty-four patients with chronic liver disease (29 men and 15 women, 49-81 years old) and 38 control subjects (17 men and 21 women, 21-79 years old) underwent dynamic CT of the spleen. Regions of interest were drawn on images of the spleen and aorta, and splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT measurement increase. In 11 patients with chronic liver disease and three patients with normal livers, we measured the wedged hepatic vein pressure (WHVP) of the right or right accessory hepatic vein to estimate portal vein pressure. RESULTS: Splenic perfusion was less in patients with chronic liver disease (0.894 +/- 0.324 ml/min) than in the control group (1.299 +/- 0.429 ml/min; p < .0001). We found a significant negative correlation between splenic perfusion and WHVP (r = .741; p = .0024). CONCLUSION: A significant decrease in splenic perfusion in patients with chronic liver disease negatively correlated with WHVP. Measurement of splenic perfusion may be useful in the evaluation of portal hypertension.     

Scopolamine injection into the olfactory bulb impairs short-term olfactory memory in rats.

A previous experiment showed that systemic administration of the muscarinic antagonist scopolamine altered delayed matching in an olfactory task in rats. The present experiment tested whether the impairment could result from blockade of the cholinergic transmission in the first relay structure of the olfactory system, the olfactory bulb. 25 rats served as Ss. The drug was infused directly into both olfactory bulbs before test sessions. Results show that the intrabulbar infusion reproduced the effect of the systemic administration. With a 4-sec delay between target odor and choice test, performances of treated rats remained unchanged; however, with a 30-sec delay, rats performed randomly. Results from a complementary electrophysiological experiment in anesthetized rats support the idea that scopolamine injected into the olfactory bulb was unlikely to have reached more central structures. Further evidence for the involvement of pure sensory areas in short-term memory is concluded. (PsycINFO Database Record (c) 2010 APA, all rights reserved)